Cytochrome P-450-mediated O-demethylation of two ellipticine derivatives. Differential effect of the murine Ah locus phenotype.

The O-demethylation of two antitumor drugs (9-methoxyellipticine and a 1-polyalkylamino-substituted analog) was studied by incubation with liver microsomes from rats and mice. The former drug underwent a cytochrome P1-450-independent biotransformation in mice, as shown by an indiscriminate response from individuals genetically responsive or nonresponsive to induction by 3-methylcholanthrene. On the other hand, the second drug was O-demethylated only by genetically responsive mice after pretreatment by 3-methylcholanthrene. It was also O-demethylated predominantly in rats pretreated with either 3-methylcholanthrene or Aroclor 1254.